title: Determination of 17q gain in patients with neuroblastoma by analysis of circulating DNA.
abstract: BACKGROUND
  Retrospective studies have demonstrated the prognostic impact of genomic profiles in neuroblastoma (NB). Segmental chromosome alterations have been found useful for identifying tumors with a high risk of relapse. As the gain of chromosome arm 17q is the most frequent chromosome alteration reported in NB primary tumors, we evaluated the presence of this 17q gain in the peripheral blood of patients with NB.
  
  
  METHODS
  Using duplex quantitative real-time PCR, we quantified simultaneously MPO (17q.23.1) and a reference gene, p53, and Survivin (17q25) and p53. MPO and Survivin copy numbers were evaluated as MPO/p53 and Survivin/p53 ratios in 142 serum or plasma samples in which 17q status had been determined by array-based comparative genomic hybridization (aCGH) or multiplex ligation-dependent probe amplification (MLPA).
  
  
  RESULTS
  In patients <18 months of age, serum-based determination of 17q gain in DNA sequences had good specificity (94.4%) and 58.8% sensitivity (P < 0.001). In contrast, for patients over 18 months of age, the approach exhibited moderate specificity (71.4%) and 51.2% sensitivity (P = ns). Similar results were observed in patients with tumors without MYCN amplification.
  
  
  CONCLUSIONS
  Our results show that 17q gain determination in circulating DNA is possible and suggest that this non-invasive test could be useful for very young children when no reliable information on genomic alterations is obtained by aCGH or MPLA analysis of tumor samples This test is complementary to previously developed techniques for detecting circulating MYCN DNA sequences.
authors.affiliation: Centre Léon Bérard, Laboratoire de Recherche Translationnelle, Lyon Cedex, France. combaret@lyon.fnclcc.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Combaret
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bréjon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Iacono
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schleiermacher
authors.forename: Gäelle
authors.initials: G
authors.lastname: Pierron
authors.forename: Agnès
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Christophe
authors.initials: C
authors.lastname: Bergeron
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.forename: Alain
authors.initials: A
authors.lastname: Puisieux
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D005784:Gene Amplification; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D051034:Inhibitor of Apoptosis Proteins / Q000097:blood / Q000235:genetics; D007377:Interleukin-3 / Q000097:blood / Q000235:genetics; D008297:Male; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D015996:Survival Rate; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000097:blood / Q000235:genetics
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D051034:Inhibitor of Apoptosis Proteins; D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000077022:Survivin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor